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Distribution of candidate genes for experimentally induced arthritis in rats
University of Borås, School of Health Science.
2010 (English)In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 11, no 146Article in journal (Refereed)
Abstract [en]

Background: Rat models are frequently used to link genomic regions to experimentally induced arthritis in quantitative trait locus (QTL) analyses. To facilitate the search for candidate genes within such regions, we have previously developed an application (CGC) that uses weighted keywords to rank genes based on their descriptive text. In this study, CGC is used for analyzing the localization of candidate genes from two viewpoints: distribution over the rat genome and functional connections between arthritis QTLs. Methods: To investigate if candidate genes identified by CGC are more likely to be found inside QTLs, we ranked 2403 genes genome wide in rat. The number of genes within different ranges of CGC scores localized inside and outside QTLs was then calculated. Furthermore, we investigated if candidate genes within certain QTLs share similar functions, and if these functions could be connected to genes within other QTLs. Based on references between genes in OMIM, we created connections between genes in QTLs identified in two distinct rat crosses. In this way, QTL pairs with one QTL from each cross that share an unexpectedly high number of gene connections were identified. The genes that were found to connect a pair of QTLs were then functionally analysed using a publicly available classification tool. Results: Out of the 2403 genes ranked by the CGC application, 1160 were localized within QTL regions. No difference was observed between highly and lowly rated genes. Hence, highly rated candidate genes for arthritis seem to be distributed randomly inside and outside QTLs. Furthermore, we found five pairs of QTLs that shared a significantly high number of interconnected genes. When functionally analyzed, most genes connecting two QTLs could be included in a single functional cluster. Thus, the functional connections between these genes could very well be involved in the development of an arthritis phenotype. Conclusions: From the genome wide CGC search, we conclude that candidate genes for arthritis in rat are randomly distributed between QTL and non-QTL regions. We do however find certain pairs of QTLs that share a large number of functionally connected candidate genes, suggesting that these QTLs contain a number of genes involved in similar functions contributing to the arthritis phenotype.

Place, publisher, year, edition, pages
BioMed Central Ltd. , 2010. Vol. 11, no 146
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:hb:diva-3069DOI: 10.1186/1471-2164-11-146Local ID: 2320/7611OAI: oai:DiVA.org:hb-3069DiVA: diva2:871165
Available from: 2015-11-13 Created: 2015-11-13

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CiteExportLink to record
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